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Updated: Jun 29, 2026
Measuring Bacterial Load and Immune Responses in Mice Infected with Listeria monocytogenes
Published on: August 9, 2011
Down regulation of macrophage IFNGR1 exacerbates systemic L. monocytogenes infection
Emily M Eshleman1, Christine Delgado1, Staci J Kearney2
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO United States of America.
Abstract:
Interferons (IFNs) target macrophages to regulate inflammation and resistance to microbial infections. The type II IFN (IFNγ) acts on a cell surface receptor (IFNGR) to promote gene expression that enhance macrophage inflammatory and anti-microbial activity. Type I IFNs can dampen macrophage responsiveness to IFNγ and are associated with increased susceptibility to numerous bacterial infections. The precise mechanisms responsible for these effects remain unclear. Type I IFNs silence macrophage ifngr1 transcription and thus reduce cell surface expression of IFNGR1. To test how these events might impact macrophage activation and host resistance during bacterial infection, we developed transgenic mice that express a functional FLAG-tagged IFNGR1 (fGR1) driven by a macrophage-specific promoter. Macrophages from fGR1 mice expressed physiologic levels of cell surface IFNGR1 at steady state and responded equivalently to WT C57Bl/6 macrophages when treated with IFNγ alone. However, fGR1 macrophages retained cell surface IFNGR1 and showed enhanced responsiveness to IFNγ in the presence of type I IFNs. When fGR1 mice were infected with the bacterium Listeria monocytogenes their resistance was significantly increased, despite normal type I and II IFN production. Enhanced resistance was dependent on IFNγ and associated with increased macrophage activation and antimicrobial function. These results argue that down regulation of myeloid cell IFNGR1 is an important mechanism by which type I IFNs suppress inflammatory and anti-bacterial functions of macrophages.
Insights
Type I interferons (IFNs) suppress macrophage antimicrobial functions by reducing IFNGR1 expression. Restoring IFNGR1 in macrophages enhances resistance to bacterial infection, revealing a key immune regulation mechanism.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Interferons (IFNs) modulate macrophage activity in inflammation and infection resistance.
- Type II IFN (IFNγ) signals through IFNGR to boost macrophage antimicrobial functions.
- Type I IFNs can impair macrophage responses to IFNγ, increasing susceptibility to bacterial infections.
Purpose of the Study:
- To investigate the mechanism by which Type I IFNs suppress macrophage responsiveness to IFNγ.
- To determine the role of myeloid cell IFNGR1 downregulation in Type I IFN-mediated immune suppression.
- To assess the impact of restored IFNGR1 on macrophage activation and host resistance during bacterial infection.
Main Methods:
- Development of transgenic mice with macrophage-specific expression of FLAG-tagged IFNGR1 (fGR1).
- Comparison of fGR1 and wild-type (WT) macrophages in response to IFNγ and Type I IFNs.
- Infection of fGR1 mice with Listeria monocytogenes to evaluate host resistance and macrophage function.
Main Results:
- fGR1 macrophages maintained cell surface IFNGR1 and showed enhanced IFNγ responsiveness in the presence of Type I IFNs.
- fGR1 mice exhibited significantly increased resistance to Listeria monocytogenes infection.
- Enhanced resistance in fGR1 mice was IFNγ-dependent and correlated with heightened macrophage activation and antimicrobial activity.
Conclusions:
- Downregulation of myeloid cell IFNGR1 is a critical mechanism for Type I IFN-induced suppression of macrophage inflammatory and antimicrobial functions.
- Restoring IFNGR1 expression in macrophages enhances host defense against bacterial pathogens.
- Targeting IFNGR1 regulation may offer therapeutic strategies for infectious diseases.
